Extinction of Conditioned Behavior:A Deoxyglucose Study

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DESCRIPTION (provided by applicant): A fundamental problem in the physiology of learning and memory is to understand the neural mechanisms of extinction and other forms of behavioral inhibition. In addition, neuroimaging investigations of extinction effects in Pavlovian paradigms are of interest because Pavlovian conditioning is impaired with aging and in Alzheimer's disease. An extinction procedure after Pavlovian conditioning is a behavioral procedure in which the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). This extinction procedure results in a decline in conditioned behavior that is known as an extinction effect. In the conditioned emotional response (CER) paradigm, a better understanding of extinction mechanisms may also have important clinical implications for using extinction in therapeutic situations, such as reduction of undesired conditioned fears. Relief from fear is a major concern in public health. Although many neural studies of extinction imply that extinction is the reversal of acquisition, the behavioral phenomena of spontaneous recovery and disinhibition suggest that this is not the case and that extinction does not result in the loss or unlearning of the CS-US association in the brain. The specific aims are to test three hypotheses: 1) The hypothesis that extinction is the opposite of acquisition, which predicts that extinction involves the loss or unlearning of the CS-US associative effects on the brain; 2) The hypothesis that extinction is a form of contextual learning, which suggests that extinction depends on neural input from both the CS and the context; and 3) Pavlov's hypothesis that extinction is a form of inhibition of the conditioned response. The brain metabolic effects of extinction will be evaluated with uptake of fluorodeoxyglucose (FDG). Metabolic data from experimental rats will be compared to those of control rats exposed to the same tone to map regional brain activity changes occurring in response to the tone CS after extinction of the CER. Brain metabolic : activity (FDG data) will also be correlated with the behavioral performance of each subject during training and testing sessions (behavioral data). It is predicted that the CER extinction effect is mainly due to the inhibition of the neural representation of the CS-CER association in the prefrontal cortex. In contrast, reversals of learning effects on other neural circuits are expected to be minor during extinction due to the savings of CS-US associative effects unrelated to CER inhibition.